DESCRIPTION: The research derives from the view that food intake within a meal is controlled by integrated afferent activity which arises from nutrient-induced coordinated activities of the GI tract. Meals terminate when the majority of ingested nutrients are still in the GI tract and not yet available for energy metabolism. The proposed experiments will identify and quantify nutrient stimulated local GI actions, identify the signals generated from these actions, determine how and where information from these various signals is integrated and assess the role of these integrated signals in the control of food intake using the satiety actions of the brain/gut peptide cholecystokinin (CCK) as a model system. The contributions of CCK elicited gastric and duodenal vagal afferent signal to CCK satiety will be evaluated. Using antisense blockade of nodose ganglia CCKA receptor synthesis, we will evaluate the specific role of vagal afferent CCKA receptors in CCK induced vagal afferent activity, CCK induced inhibition of gastric emptying and CCK satiety. In primates, the quantitative contribution of endogenous CCK to the control of gastric emptying of various nutrients at multiple concentrations will be evaluated. The macronutrient specific contributions to duodenal/gastric feedback and how feedback signals generated by single nutrients coordinate to determine gastric emptying of nutrient combinations will be quantified. In rats, the roles of vagal and sympathetic afferent fibers in the coordination of gastric emptying will be assessed and related to food intake within a meal. Nutrient gastric emptying as integrated patterns of transpyloric flow will be characterized and relationships between pulse magnitude and interpulse intervals will be identified with a variety of nutrients. The dynamics of transpyloric flow to simultaneous microstructural analysis of food intake will be related.